Parasitic Worms Wiggle into Modern Medicine

In 2006, a man named Jasper Lawrence travelled to Africa to infect himself with hookworm by walking barefoot in a steaming mound of human excrement. He and other proponents of so-called helminthic therapy say that industrialized societies have become too clean, and in the process of sterilizing our homes and bodies, we’ve eradicated an essential piece of our biology: intestinal worms.

Hookworms attached to the intestinal mucosa. (Source: CDC)

The therapy requires the deliberate infection with helminths, or parasitic worms, by swallowing them or letting them crawl through the skin. It claims to alleviate a range of autoimmune and inflammatory diseases like allergies, inflammatory bowel diseases (IBD) and multiple sclerosis (MS). The Food and Drug Administration has not approved helminthic therapy. Nonetheless, Lawrence formed an online business in 2007 selling homegrown worms to autoimmune disease suffers around the world; he now operates out of the U.K.

Companies like Lawrence’s are relatively new, but researchers have been looking at parasitic worms and their effects on the immune system for decades. William C. Gause, director of the Center for Immunity and Inflammation at Rutgers University, began studying autoimmune diseases and helminthic therapy in the 1980s, and it has been a focus of his work since 2004. I recently had the opportunity to ask Gause a few questions about progress in the field; his responses follow.

Helminthic therapy is mainly used to treat IBD, like ulcerative colitis and Crohn’s disease. Can you describe any particularly compelling evidence of its success with these diseases?

There was an individual in California who had severe IBD. The standard treatment of steroids wasn’t effective for him, so he went to Thailand and got a doctor to infect him with human Trichuris trichiura [whipworm] and he got better right away, which is kind of amazing.

William C. Gause

The parasite only stays in the body for a few years, so when it disappeared, he started to come down with IBD again. He went to UC San Francisco and they offered him treatments, but he wasn’t getting better. So they said if you go back to Thailand and get infected again, we’ll track you. Of course this is all anecdotal, but sure enough, after he got infected, he got better again.

A researcher named P’ng Loke collected biopsies of his intestine and colon, and he found some very interesting changes in the immune response in his gut. The parasite seemed to play an important role in regulating harmful inflammation. Loke published a paper on it in Science Translational Medicine in 2010. It was very exciting research.

What are some of the key recent advances in the study of helminthic therapy?

The development of the Type 1/Type 2 paradigm was very important in the late 1980s. It became clear that we have two different kinds of immune responses. The Th1 [Type 1] response follows infection with viruses and bacteria, triggering elevations in specific cytokines [immune system secretions that affect other cells].

The Th2 [Type 2] response is another kind of immune response following infection with helminths. It has a lot of similarities, but also differences, with the response triggered by allergens.

So parasites and allergens both trigger the same type of immune response, a Th2 response, but parasites seem to calm the immune system, and allergens exacerbate it. Why is that?

Although they may appear contradictory at first, because in both cases they’re triggering the Th2 response, one of the differences is that the response to helminths may have more regulatory components [immune system substances that suppress immune responses]. It’s now become clear that helminth infection triggers a Th2 response and elevations in regulatory cell populations. It’s these two together which really form the protective response against helminth parasites.

Hookworm in the intestines. (Illustration courtesy of SCIEPRO)

Can you describe this “protective response”?

When these parasites migrate through tissues, they can cause considerable damage by forcing themselves through cells and secreting damaging enzymes. But [helminth infection] triggers important wound healing components, which help tolerate the parasite.

The protective response can be divided into two categories. One is resistance, which eventually expels the parasite. And the other is tolerance, which allows us to live with the parasite and control the damage it may be causing. You don’t see this so much in allergic responses. Allergic responses are kind of like a Th2 response that’s run amok. It lacks the regulatory controls that are present following helminth infection.

Helminthic therapy claims to treat a wide variety of diseases like MS, IBD, diabetes, allergies and even autism. Are all of these diseases related?

Yes, they are. All of those diseases have an immune response that’s gone awry, resulting in harmful inflammation. What really stands out in diseases like MS, Type I diabetes and IBD is the Th1 immune response. It’s a common thread that seams throughout all these different diseases.

If it turned out that harmful inflammation was an important aspect of autism, it may be that the helminth-induced Th2 immune response, the regulatory component, may be able to control the inflammation.

Proponents of helminthic therapy say that exposure to intestinal parasites early in life may be beneficial for our immune systems. Why is that?

You have to think about parasites living chronically in hosts, and the co-evolutionary dynamic occurring as a result of these chronic infections. One model would be that this shapes the immune response starting at a very early stage of development in children. And what it might do is trigger components that control harmful inflammation.

So should we expose our children to helminths at a young age?

I don’t think we know enough at this point. We have to do more tests. I think it’s got potential. It might be a way to trigger regulatory components that perhaps inhibit harmful autoimmune and inflammatory diseases. I think it should be an active area of research that we have to look into.

Courtesy of Elke Van de Velde

The current infection process is a bit… gross. Therapy users either drink worm larvae or let them crawl through their skin. Are there any possible alternative modes of infection?

Another approach would be to not only use helminths, but to use products from helminths. If we can understand what it is about the helminths that’s actually triggering these regulatory immune components, we can use that instead of a live helminth.

Why don’t you think enough studies have been done already?

It’s only fairly recently that we’ve begun to do clinical trials with helminths or helminth products. Clinical trials take years to be performed and completed. I don’t think it’s a lack of funding, I think it’s just going through a natural progression right now.

How has the FDA responded to the use of parasites in human clinical trials?

They approved TSO [Trichuris suis ova, or whipworm eggs] as an investigational new drug, which allowed us to move forward with clinical trials. TSO was made under GMP [Good Manufacturing Practices], and has been used in clinical trials over the last few years. It was one of the first to go through the clinical trial system. We hope we can study them more.

What are the major challenges that remain in approving a worm therapy?

Time is the main challenge. We can always use more funding, but I don’t want to say that there isn’t support for this.

Does anyone disagree with helminthic therapy?

There’s always the “ick” factor involved in giving people helminths. But I think the idea of being able to harness the regulatory components of the Th2 immune response that’s initially stimulated by helminths is pretty widely accepted as an exciting direction to go in.

How dangerous is self-infection with parasites. Is it safe to buy worms online?

I would have concerns with going out there and treating individuals with live helminths that are not standardized, or that cannot be repeated from one batch to the next. We don’t want to jump too far ahead and get into some of these treatments that are not at that level of development. Let’s make sure it works with experimental models, and then move on to phase I clinical trials, then phase II clinical trials, then see the outcome.

After studying these worms for so long, would you infect yourself if you had one of these autoimmune diseases?

Despite tantalizing anecdotal information, I would be skeptical about doing it because we don’t have standardized treatments yet. The more I think about it – the side effects, where did the worm come from, what bacteria does it have associated with it – all of these are real risk factors. I would advise everyone to be patient, let it work its course. It may end up that it works with certain inflammatory diseases and not others. It’s something we have to explore over the next decade or so to really let it go forward in treating the general public.

The views expressed are those of the author and are not necessarily those of Scientific American.

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